Modulation of the Host Lipid Landscape to Promote RNA Virus Replication: The Picornavirus Encephalomyocarditis Virus Converges on the Pathway Used by Hepatitis C Virus

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All positive-sense RNA viruses [(+)RNA viruses] replicate their viral genomes in tight association with reorganized membranous structures. Viruses generate these unique structures, often termed “replication organelles” (ROs), by efficiently manipulating the host lipid metabolism. While the molecular mechanisms underlying RO formation by enteroviruses (e.g. poliovirus) of the family Picornaviridae have been extensively investigated, little is known about other members belonging to this large family. This study provides the first detailed insight into the RO biogenesis of encephalomyocarditis virus (EMCV), a picornavirus from the genus Cardiovirus. We reveal that EMCV hijacks the lipid kinase phosphatidylinositol-4 kinase IIIα (PI4KA) to generate viral ROs enriched in phosphatidylinositol 4-phosphate (PI4P). In EMCV-infected cells, PI4P lipids play an essential role in virus replication by recruiting another cellular protein, oxysterol-binding protein (OSBP), to the ROs. OSBP further impacts the lipid composition of the RO membranes, by mediating the exchange of PI4P with cholesterol. This membrane-modification mechanism of EMCV is remarkably similar to that of the distantly related flavivirus hepatitis C virus (HCV), while distinct from that of the closely related enteroviruses, which recruit OSBP via another PI4K, namely PI4K IIIβ (PI4KB). Thus, EMCV and HCV represent a striking case of functional convergence in (+)RNA virus evolution.

Vyšlo v časopise: Modulation of the Host Lipid Landscape to Promote RNA Virus Replication: The Picornavirus Encephalomyocarditis Virus Converges on the Pathway Used by Hepatitis C Virus. PLoS Pathog 11(9): e32767. doi:10.1371/journal.ppat.1005185
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005185

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